NM_000251.3(MSH2):c.2558A>G (p.Glu853Gly) AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 13, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000524394.10

Allele description [Variation Report for NM_000251.3(MSH2):c.2558A>G (p.Glu853Gly)]

NM_000251.3(MSH2):c.2558A>G (p.Glu853Gly)

Gene:

MSH2:mutS homolog 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2p21

Genomic location:

Preferred name:

NM_000251.3(MSH2):c.2558A>G (p.Glu853Gly)

Other names:

p.E853G:GAG>GGG

HGVS:

NC_000002.12:g.47480795A>G
NG_007110.2:g.82672A>G
NM_000251.3:c.2558A>GMANE SELECT
NM_001258281.1:c.2360A>G
NP_000242.1:p.Glu853Gly
NP_000242.1:p.Glu853Gly
NP_001245210.1:p.Glu787Gly
LRG_218t1:c.2558A>G
LRG_218:g.82672A>G
LRG_218p1:p.Glu853Gly
NC_000002.11:g.47707934A>G
NM_000251.1:c.2558A>G
NM_000251.2:c.2558A>G

Protein change:

E787G

Links:

dbSNP: rs63750797

NCBI 1000 Genomes Browser:

rs63750797

Molecular consequence:

NM_000251.3:c.2558A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001258281.1:c.2360A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary nonpolyposis colorectal neoplasms
Identifiers:: MeSH: D003123; MedGen: C0009405

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000548278	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 13, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 21642682, 23047549, 25559809, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000548278

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 13, 2022)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome.

Bonadona V, Bonaïti B, Olschwang S, Grandjouan S, Huiart L, Longy M, Guimbaud R, Buecher B, Bignon YJ, Caron O, Colas C, Noguès C, Lejeune-Dumoulin S, Olivier-Faivre L, Polycarpe-Osaer F, Nguyen TD, Desseigne F, Saurin JC, Berthet P, Leroux D, Duffour J, Manouvrier S, et al.

JAMA. 2011 Jun 8;305(22):2304-10. doi: 10.1001/jama.2011.743.

PubMed [citation]

PMID:: 21642682

Frequency of mutations in mismatch repair genes in a population-based study of women with ovarian cancer.

Pal T, Akbari MR, Sun P, Lee JH, Fulp J, Thompson Z, Coppola D, Nicosia S, Sellers TA, McLaughlin J, Risch HA, Rosen B, Shaw P, Schildkraut J, Narod SA.

Br J Cancer. 2012 Nov 6;107(10):1783-90. doi: 10.1038/bjc.2012.452. Epub 2012 Oct 9.

PubMed [citation]

PMID:: 23047549
PMCID:: PMC3493867

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000548278.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 853 of the MSH2 protein (p.Glu853Gly). This variant is present in population databases (rs63750797, gnomAD 0.0009%). This missense change has been observed in individual(s) with colorectal cancer (PMID: 21642682, 23047549, 25559809). ClinVar contains an entry for this variant (Variation ID: 91000). Advanced modeling of experimental studies (such as gene expression, population dynamics, functional pathways, and cell-cycle effects in cell culture) performed at Invitae indicates that this missense variant is not expected to disrupt MSH2 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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